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Beta blockers do not increase the risk of depression, fatigue, or sexual problems, according to researchers who analyzed 15 studies involving more than 35,000 patients who took beta blockers to treat heart attack, heart failure, or hypertension. This is important because beta blockers can benefit many patients, but many doctors do not prescribe them., Context: [beta]-Blocker therapy remains substantially underused in cardiac patients despite its proven mortality benefits. Reluctance to prescribe these agents may derive from concerns about their association with symptoms of depression, fatigue, and sexual dysfunction. Objective: To determine the association of [beta]-blockers with depressive symptoms, fatigue, and sexual dysfunction by performing a quantitative review of randomized trials that tested [beta]-blockers in myocardial infarction, heart failure, and hypertension. Data Sources: Randomized trials of [beta]-blockers used in the treatment of myocardial infarction, heart failure, or hypertension were identified by searching the MEDLINE database for English-language articles (1966-2001). In addition, we searched the reference lists of previously published trials and reviews of [beta]-blockers for additional studies. Study Selection: Criteria for inclusion of trials in the review were: random allocation of study treatments, placebo control, noncrossover design, enrollment of at least 100 patients, and a minimum of 6 months of follow-up. The initial search produced 475 articles, 42 of which met these criteria. Fifteen of these trials reported on depressive symptoms, fatigue, or sexual dysfunction and were selected for inclusion. Data Extraction: For each trial, 1 author abstracted the frequency of adverse events in the [beta]-blocker and placebo groups and the numbers of patients randomized to the treatment groups. Two other authors verified the counts of events, and all authors adjudicated any discrepancies. Two different types of information on adverse events were abstracted: patient-reported symptoms and withdrawal of therapy due to a specified symptom. We categorized the tested [beta]-blockers by generation (early vs late) and lipid solubility (high vs low to moderate). Data Synthesis: The 15 trials involved more than 35000 subjects. [beta]-Blocker therapy was not associated with a significant absolute annual increase in risk of reported depressive symptoms (6 per 1000 patients; 95% confidence interval [CI], -7 to 19). [beta]-Blockers were associated with a small significant annual increase in risk of reported fatigue (18 per 1000 patients; 95% CI, 5-30), equivalent to 1 additional report of fatigue for every 57 patients treated per year with [beta]-blockers. [beta]-Blockers were also associated with a small, significant annual increase in risk of reported sexual dysfunction (5 per 1000 patients; 95% CI, 2-8), equivalent to one additional report for every 199 patients treated per year. None of the risks of adverse effects differed significantly by degree of [beta]-blocker lipid solubility. The risk associated with reported fatigue was significantly higher for early-generation than for late-generation [beta]-blockers (P=.04). Conclusion: The conventional wisdom that [beta]-blocker therapy is associated with substantial risks of depressive symptoms, fatigue, and sexual dysfunction is not supported by data from clinical trials. There is no significant increased risk of depressive symptoms and only small increased risks of fatigue and sexual dysfunction. The risks of these adverse effects should be put in the context of the documented benefits of these medications.

Statin drugs appear to be very effective in lowering cholesterol levels and reducing death rates from cardiovascular disease. These drugs include lovastatin, pravastatin, and simvastatin. Researchers reviewed 16 clinical trials covering about 29,000 patients who were taking one of these drugs. On average, total cholesterol levels were reduced by 22% and low-density lipoprotein cholesterol levels by 30%. Statins reduced the risk of stroke 29% and overall death rates by 22%. Death rates from cardiovascular disease were reduced 28%., Objective.--To examine whether cholesterol lowering with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statin drugs) reduces the risks of stroke and total mortality. Data Sources.--We conducted a computerized literature search from 1985 through 1995 to identify all published trials testing statin drugs. The Cholesterol and Recurrent Events (CARE) data were added after the report was published in October 1996. Our search was limited to English-language articles and included published overviews containing relevant individual trials. Trial Selection.--Criteria for inclusion of randomized trials in the overview were (1) statin drugs alone used to reduce lipid levels rather than multifactorial interventions including another type of cholesterol-lowering drug and (2) inclusion of data on deaths and/or strokes. Data Extraction.--Data were extracted by 2 researchers, and only minor discrepancies, which were easily resolved by discussion, occurred. Principal investigators of the trials and their funding agencies were also contacted to secure any relevant data not included in the published reports. Data Synthesis.--A total of 16 individual trials including approximately 29 000 subjects treated and followed up an average of 3.3 years were included in the overview. The average reductions in total and low-density lipoprotein cholesterol achieved were large--22% and 30%, respectively. A total of 454 strokes (fatal plus nonfatal) and 1175 deaths occurred. Those assigned to statin drugs experienced significant reductions in risks of stroke of 29% (95% confidence interval [CI],14%-41%) as well as total mortality of 22% (95% CI, 12%-31%), which was attributable to a significant reduction in cardiovascular disease (CVD) deaths of 28% (95% CI, 16%-37%). There was no evidence of any increased risk in non-CVD mortality (relative risk [RR], 0.93; 95% CI,0.75-1.14). There was also no significant increase in risk of cancer (RR, 1.03; 95% CI, 0.90-1.17). Conclusion.--This overview of all published randomized trials of statin drugs demonstrates large reductions in cholesterol and clear evidence of benefit on stroke and total mortality. There was, as expected, a large and significant decrease in CVD mortality, but there was no significant evidence for any increases in either non-CVD deaths or cancer incidence. JAMA. 1997;278:313-321

There appears to be no statistically significant link between breast implants and connective tissue disease. Connective tissue disease includes rheumatoid arthritis, systemic lupus erythematosus and scleroderma. Researchers sent a questionnaire to 395,543 women participating in the Women's Health Study asking whether they had ever been diagnosed with a connective tissue disease and whether they ever had a breast implant. Women who had received a breast implant were 24% more likely to have any connective tissue disease, but the risks of having a specific connective tissue disease were generally not statistically significant. There was no increased risk with greater exposure to the implants nor with greater age., Objective.--To evaluate the association of breast implants with connective-tissue diseases. Design and Participants.--Retrospective cohort study of 395 543 female health professionals who completed mailed questionnaires for potential participation in the Women&apos;s Health Study. A total of 10 830 women reported breast implants and 11 805 reported connective-tissue diseases between 1962 and 1991. Cox proportional hazards regression models were used in analyses. Main Outcome Measure.--Self-reported connective-tissue diseases. Results.--Compared with women who did not report breast implants, the relative risk (RR) of the combined end point of any connective-tissue disease among those who reported breast implants was 1.24 (95% confidence interval, 1.08 to 1.41, P-.0015). With respect to the individual diseases, the finding for other connective-tissue diseases (including mixed) was statistically significant (P--.017), the findings for rheumatoid arthritis, Sjogren&apos;s syndrome, dermatomyositis or polymyositis, or scleroderma were of borderline statistical significance (.05< P

Abstract Background To examine interactions among the angiotensin converting enzyme (ACE) insertion/deletion, plasminogen activator inhibitor-1 (PAI-1) 4G/5G, and tissue plasminogen activator (t-PA) insertion/deletion gene polymorphisms on risk of myocardial infarction using data from 343 matched case-control pairs from the Physicians Health Study. We examined the data using both conditional logistic regression and the multifactor dimensionality reduction (MDR) method. One advantage of the MDR method is that it provides an internal prediction error for validation. We summarize our use of this internal prediction error for model validation. Results The overall results for the two methods were consistent, with both suggesting an interaction between the ACE I/D and PAI-1 4G/5G polymorphisms. However, using ten-fold cross validation, the 46% prediction error for the final MDR model was not significantly lower than that expected by chance. Conclusions The significant interaction initially observed does not validate and may represent a type I error. As data-driven analytic methods continue to be developed and used to examine complex genetic interactions, it will become increasingly important to stress model validation in order to ensure that significant effects represent true relationships rather than chance findings.